Pyridyl phenyl-carbamate rodenticide

ABSTRACT

3-Pyridylmethyl N-(4&#39;&#39;-substitutedmercaptophenyl) carbamates and their acid salts and metal salt complexes useful as a rodenticide.

United States Patent Kilbourn et al.

[ 1 Dec. 30, 1975 PYRIDYL PHENYL-CARBAMATE RODENTICIDE Inventors: Edward E. Kilbourn, Chalfont;

Ernest D. Weiler, Ambler, both of Pa.

Assignee: Rohm & Haas Company,

Philadelphia, Pa.

Filed: Dec. 28, 1973 Appl. No.: 429,464

U.S. Cl. 2'60/294.8 G; 260/270 R; 260/295.5 R; 424/84; 424/263 Int. Cl. C07D 213/75 Field of Search 260/294.8 G, 295 CA, 295.5 C

Primary ExaminerAlan L. Rotman 57 ABSTRACT S-Pyridylmethyl N-(4'-substitutedmercaptophenyl) carbamates and their acid salts and metal salt complexes useful as a rodenticide.

5 Claims, No Drawings PYRIDYL PHENYL-CARBAMATE RODENTICIDE The present invention relates to B-pyridylmethylN- (4'-mercaptophenyl)carbamate and certain of its mercapto derivatives and more particularly to their use and of compositions containing them for the control and extermination of pest rodents. This includes their salts and complexes.

The common rat, Rattus norvegicus, is viseious and constantly poses a serious threat to the health and weli being of man. Rats and mice are destructive animals and a serious nuisance, causing millions of dollars damage annually to farms, agronomic crops, homes, food processing plants and many other businesses. Rats bite at least 14,000 (possibly up to 60,000) people every year, according to the US. Public Health Service, and are known carriers of over 35 contagious diseases including bubonic plague, trichinosis, typhus, rat bite fever, amoebic dysentery, tuberculosis, infectiousjaundice and rabies. During the years from 1898 to 1923, almost 11 million deaths were caused by rat-borne plaques.

Use of rodenticides, fumigants, sprays and traps are the primary methods employed for the control of pest rodents. The term pest rodents refers not only to members of the order Rodentia but also to those of lagomorpha, which cause health hazards or economic loss unless kept in check. Rodenticides may be used in the form of a tracking powder or a bait or may be applied as a spray on the rodents natural foodstuffs. The rodenticides used as a bait are of two classes: singleand multi-dose, Multi-dose rodenticides are usually selected over single-dose rodenticides, as they have been safer in the past than the available single-dose rodenticides. The multi-dose rodenticides are anticoagulants, including a number of different 4-hydroxycoumarin and 1,3-indandione compounds. These multi-dose rodenticides consumed in small daily amounts have a lethal effect on rats and mice after liver stores of vitamin K have been depleted. Anti-coagulants are less effective on mice than rats, as mice are considered to bc nibblers and may not consume an adequate amount of treated bait to have a lethal effect. A single-dose rodenticide which would be relatively safe to the person handling the material and to non-target species of animals and yet effective on a variety of pest rodents is highly desirable.

Many compounds are toxic to rodents. However, very few of these compounds are anywhere near suitable for use as a rodenticide because it is necessary for the pest rodent to consume voluntarily a sufficient amount of the poison even though sufficient untreated food may also be available. In bait rodenticides, feed acceptance is the key to excellence, and in all rodenticides safety and efficacy are highly important.

The 3-pyridylmethyl N-(4'-mercaptophenyl)carbamate and its derivatives of the present invention are so highly toxic to a wide variety of pest rodents that a single dose is sufficient; yet they are relatively safe for use in the presence of other species which may inadvertently ingest limited quantities of the rodenticide. Furthermore, rats and other pest rodents willingly consume the compounds in sufficiently lethal amounts when present in baits. Alternatively the compounds may be employed in compositions to be sprayed on natural foodstuffs. They may also be employed in a 2 tracking powder, especially for use against mice, which habitually clean their paws by licking.

The basic compounds of the present invention have the formula:

. NCO

3-Pyridylcarbinol is a product of commerce. The RS- substituted phenyl isocyanates may be readily made by standard procedures.

The following typical examples describe variations in the preparation of 3-pyridylmethyl N-(4-mercapto phenyl)carbamate and its various derivatives.

EXAMPLE 1 Preparation of 3-pyridylmethyl N-(4-mercaptophenyl)carbamate p-Mercaptophenyl isocyanate (0.9g, 0.00595 mole) was added to a solution of 3-pyridyl carbinol (0.65g., 0.00595 mole) in 50 ml. of benzene and the reaction mixture was allowed to stand over the weekend. It was then heated to reflux to assure completion of the reaction and then cooled to give a white solid. This was isolated as 1.2g. and was a 78% yield of 3-pyridylmethyl N-(4'-mercaptophenyl)carbamate.

EXAMPLE 2 Preparation of 3-pyridylmethyl N-(4'-methylthiophenyl)carbamate To a solution of 4.4g. (0.04 mole) of 3-pyridyl carbinol in 50 ml. of benzene containing 0.1g. of Dabco catalyst was added, dropwise, a solution of 6.6g. (0.04 mole) of p-methylthiophenyl isocyanate (New Haven Chemicals) in 50 ml. of benzene. During the addition a white solid separated and the temperature rose from 23 to 34C. The mixture was stirred at ambient temperature for 16 hrs. and the product was filtered off. After oven-drying in vacuo there was obtained 10.4g. melting at 133-l35C. This is a yield of 3-pyridylmethyl N-(4-methylthiophenyl)carbamate.

EXAMPLE 11 Preparation of 3-pyridylmethyl N-(4-thiocyanophenyl )carbamate To a solution of p-thiocyanophenyl isocyanate (5.25g., 0.0298 mole) in 100 ml. of benzene was added 3-pyridyl carbinol (3.25g., 0.0298 mole). An immediate exothermic reaction took place and a solid precipitated. After standing over the weekend 5.5g. of solid wherein R has the meanings defined above or an alkyl group of l to 5 carbon atoms M is a cation of a metal such as cadmium, calcium, cobaltous, cupric, ferrous, ferric, manganous, mercuric, nickel, silver, stannous and zinc, X is an anion forming a compound with the cation M in which the compound has sufficient solubilwas isolated and after recrystallization from toluene 1O l to form acomple,x with theFomPollnds oftheinven this gave melting at o o This was a 47% tlon such as bromide, chloride, iodide, perchlorate, yield of 3 pyridylmethyl N (4r thiocyanophenyl)carba carbonate, bicarbonate, nitrate, phosphate, sulfate, mate b1sulfate, acetate, maleate, oxalate and p-toluenesulfonate, a is an integer corresponding to the valence of EXAMPLE 13 15 cation M and n is an integer which for the anion X Preparation of 3 pyridylmethyl satlsfles the valence of the cation M. (5 etra o y rcap op yl)Carba ate The preparation of 3-pyrldylrnethyl N-(fl methylth1- ophenyl)carbamate hydrochloride is typical of these A lreaFtlon mlxture conslstmg of 'py y y acid salts. Gaseous HCl was passed into a solution of y p y 8- 20 5g. of 3-pyridylmethyl N-(4-nitrophenyl)carbamate in mole) 599mm 21198 9 8- mole) and 50 of 100 ml. of acetone. A solid formed and after filtration, pp dlmethylf9l'mam1de was heated to reflulf washing and drying in a vacuum oven this amounted to the, after Standmg Over the weekend was 5.0g. of solid. This was found by analysis to contain heated another 2 hrs. then concentrated in vacuo. The C, H, 1 55% N and 21 54% l resldual oll was slurr1ed in 100 ml. of water, acidified to 25 lated f CI3HHN3Q4 HBr is 44 09% C 342% H, P 2 12N H and filtered; The residue was 11.86% N and 22.56% Br. The product is an 88% yield fY F p p to yleld gof recrystal' of 3-pyridylmethyl N-(4'-methylthiophenyl)carbamate llzed solld meltlng at l l8l94C with decomposition. hydrochloride Thls 18% yleld of 'Py y y A typical preparation for a metal salt complex of the y f p P y carbamatecompounds of the invention is as follows. To a solution Also included 1n the compounds of this invention are f 0 (0 0183 mole) f 3 1 1 N 4' the F addition Salts and metal Salt complexes of methylthiophenyl) carbamate in 300 ml. of methanol gpy y f y 'mel'captophenyl)carbamate and was added a solution of l.2g. (0.0091 mole) of anhylts 4'-subst1tuted-mercapto derivatives. These also are drous ZnC]2 in 0 1 f methanoL The resulting excellent rodefmlcldes- I cipitate was isolated by filtration and drying to give The -Py y y ap 5.3g. of solid melting at 209-2l 1c. The product was phenyll-carbarnates can form novel acid salts with a an 3% yield f 3 pyridy1methy| 4' 1 i strong lnorganlc or organ1c acid. Typlcal strong acids phenyncarbamateiinc chloride complex mfilude y p r bydrochloncr y f r The following Tables I and [I give physical constants Ph p sum-Inc, 'chloroacetlcr Oxallc, malelc 40 for the intermediate phenyl isocyanates and for typical Succmlc and p'toluenesulfomcnovel carbamates of this invention.

The novel metal salt complexes may be depicted by the structure Table I 4-RSCGH4NCO Intermediates Used in Example SR= Boiling Point C/Pressure l SH S66l/O.85 I I 2 -SCH a commercial product 3 SC H 67-72/O.25 4 -SC H-,-n -95/O.4 so a iiil'im CHQOCUDNIv SR 7 :SClHzlso 0.25 8 SC H -sec 7882/0.25 9 sc,,11,,-ri 104-124/0.2s N [0 --S allyl 778l/0.l

l l SCN brown oil* 55 12 SCCL1 brown oil a Identified by the infrared spectrum Table II Typical 3-Pyridylmeihyl N-(4'-RS-phenyl)carbamate Melting Empirical Analysis Example R= Point (C) Formula C H N l H 166-1695 c l-l mms 59.8(60.0) 4.3(4.6) l0.5( l0.8) 2 CH3 133-l35 C H N O S 6l.3(6l.3) 5.0(5.l) lO.Z(l0.2) 3 C2H5 l l6-l l9 CHHWNZOQS 62.5(62.3) 5.6(5.5) 9.4(9.7) 4 n-C H l24-l26 c ,l-1,..N o,s 63.3(63.6) 6.l(6.0) 9.l(9.3) 5 iso-C H 103-107 C H N O S 63.7(63.6) 6.0(6.0) 9.S(9.3) 6 n-C H ll5-l l7 C|,H0N,O2S 64.5(64.5) 6.4(6.4) 8.8(8.9) 7 iso-C H lOO-l04 CHHNNZOZS 64.7(64.5) 6.4(6.4) 8.8(8.9)

Table II-contmued Typical 3-Pyridylmethyl N-(4'-RS-phenyl)carbamate Melting Empirical Analysis* Example R= Point (C) Formula C H N 8 sec-C H l 13-] C H N O S 64.4(64.5) 6.4(6.4) 8.9(8 9) 9 n-C H 96.5-102 C ,,H .,N o,s 65.7(66.3) 7.1 7.0 8.4(8 1) l0 allyl 96-99 c n N o s 63.8(64.0) 5.4(5.4) 9.2(9.3) l1 CN 188-191 C H,,N O S 58.9(58.9) 3.8(3.9) 14.5( 14.7) [2 CCl: 153-155(dec.) C, H Cl N O S 44.8(445) 3.l(2.9) 7.4(7.4) l3 S-tetrazolyl l88l94(dec.) C H N O S 51 .3(51.2) 3.7(3.7) 24.7(25.6) 14 HCl salt of 193-195(dec.) C I-I N O S 54.3(54.l) 5.2 4.9 8.8(9.0)

Example 2 .I-ICl l5 Oxalic acid 209-21 l(dec.) C H N O S 52.9(52.7) 4 5(4.4) 7.6(7.7)

salt of Example 2 .(COOH) 16 Zinc chloride l54l56(dec.) C H N O S complex of Example 2 .l/Z ZnCl- 49.2(49.l) 4.3(4.I) 8.I(8.2)

The number in parenthesis represents the theoretical value as calculated from the empirical formula The 3-pyridylmethyl N-(4'-mercaptophenyl)carbamate and its 4-substituted mercapto derivatives and salts and complexes of the present invention may be formulated into rodenticidal compositions such as baits, tracking powders, and sprays. A bait comprises a used as the sole toxicant in baits, the compounds of the present invention may be used in any rodenticidally effective concentration.

Depending on the susceptibility of the rodents to the toxicant and the amount of formulated bait generally consumed, concentrations as flow as 0.1%, and especially when intended for mice, even lower than 0.05% may be employed. A typical bait may contain between about 0.5 and 1.5% of the toxicant by weight. Surprisingly it has been found that there ia no upper limit to the amount of compound which may be present in a bait; hence, the bait can contain from 0.l to 100% of the toxicant. Rats, mice and other rodents accept the compounds of the present invention so well that even when offered free choice between untreated basal ration and a bait consisting entirely of it, they ingest rodenticidally sufficient quantities of the toxicant. An example below describes the formulation of a suitable bait, although wide variations in formulation for different conditions of use are of course expected.

BAIT FORMULATION A 3-pyridylmethyl N-(4-substituted-mercaptophenyl) carbamate was blended with the basal ration in a Waring laboratory blender to form 50 grams of a homogeneous premix. The amount of compound utilized was determined by the percentage of active material desired in the feed. The formula for the basal ration is shown below, all percentages being by weight:

Crude ground corn 65% Steel cut oats 25% Powdered sugar 5% Corn oil 5% The 50 grams of premix containing the toxicant were then mixed with an additional 450 grams of basal ration. These components were mixed in a Little Ford Lodige mixer for 3 minutes.

Tracking powders, which are particularly effective against mice, may be either a compound of the present invention in finely powdered form or a mixture of the compound with powdered carrier, e.g., talc, su'gar, milk powder, Indian corn meal, fish meal, cornstarch, flour, and bentonite, or the like, or any combination thereof which tends to induce the animals contaminated with the preparation to lick themselves more thoroughly. In tracking powders, a compound of the present invention may be incorporated in amounts from down to 0.1% by weight with proper formulation. An example below describes the preparation of a suitable tracking powder.

TRACKING POWDER Table III Preliminary Rodenticidal Activity Acute oral toxicity (50 mg./kg.)

Example rats dead/rats in test 1 2/2 (within 8 days) 2 2/2 (with 4'hours) 3 2/2 (within 8 days) 4 2/2 (within 24 hours) 5 2/2 (within 24 hours) 6 2/2 (within 8 days) 7 2/2 (within 8 days) 8 2/2 (within 8 days) 9 O/2 (at 100 mgJkg.) 10 2/2 (within 24 hours) 1 l 2/2 (within 24 hours) 12 2/2 (within 8 days) 13 2/2 (within 8,days) 14 2/2 (within 3 hours) 15 2/2 (within 3 hours) 16 212 (within 3 hours) One of the most significant secondary tests is a standard one known as the paired-preference test. In this 7 test the rodents are given a free choice between the treated and untreated bait in individual cages or in a communal tank. Such a test most nearly approximates Table IV Paired-Preference Test of 3-Pyridylmethyl N-(4'-methylthiopheny1)carbamate Using Individually Caged Rodents Compound in Basal Ration Rodents Rodents Rodent Species (parts per millions) killed in in test 8 days a) albino rat 100,000 4/4 50,000 2/2 10,000 4/4 3,000 4/4 1,000 4/4 500 4 4 300 4/4 100 2/ 50 /4 b) Norway rat 100,000 4/4 10,000 4/4 5,000 4/4 2,500 19/20 2,500 4/4 1,250 4/4 625 3/ 2,500* 20/20 c) roof rat 100,000 4/4 (Ratlu: ratlus) 10,000 4/4 5,000 3/4 2,500 4/4 2,500 19/20 1,250 3/4 625 2/4 312 0/4 d) feral mice 100,000 4/4 (Mus musculus) 10,000 4/4 5,000 4/4 2,500 4/4 1,250 3/4 625 2/4 312 4/4 156 4/4 75 0/ e) deer mice 100,000 4/4 (Peromyscus .rpp.

10,000 4/4 5,000 4/4 2.500 4 4 2,500 19/20 1 1,250 3/ 625 312 /4 f) ground moles 2,500 2/2 (Microtus spp.) 2,500 1 8/20 In communal tank practical use conditions.

When caged individually, they were provided with dual feed cups and separate water devices. When caged in a communal tank, they were offered'a multiplicity of feed cups and water devices. The basal ration was offered in excess of daily feed requirements in each of two feeders; one treated with the test compound and one without. For each test, equal numbers of each sex were used.

The gross weight of each feed container and its feed were determined daily and returned to the starting weight by addition of complete replacement of the given diet. The position of the bait and the laboratory diet cups in the cage were reversed every 24 hours to counter any feeding position habit of the rat. The test rodents had free choice between treated and untreated feed. Mortalities were recorded daily.

To meet the criteria for a single-dose product, a rodenticide in this initial test must kill 75% of the rats within 8 days, where the poison bait is available for the first 72 hours of this period.

Another secondary testing procedure is known as the tracking test. In this test the rodents are permitted to walk over areas on which the tracking powder has been placed. One such procedure follows:

Mouse Tracking Test with B-pyridylmethyl N-(4'-methylthiophenyl)carba-- mate are shown in Table V.

Table V Tracking Test Using Feral Mice Compound in Tracking Powder Mice killed within 8 days Mice in test 9 10 Table V-continued whcrem R a. hydrogen Tracking Test Using Feral Mice b n l Compound in Tracking Powder Micc killed within Mice in a y 8 days test C. CN 5% 4/4 Or 5 4/4 1.25% e. tetrazolyl 625% 4/4 and its acid salts.

It: 2. A compound selected from the group consisting of A 0 the compound according to claim 1 in which R is CN and its acid salts.

We claim: 3. A compound selected from the group consisting of 1. A Compound of the Structure the compound according to claim 1 in which R is 5-tetrazolyl and its acid salts.

4. A compound selected from the group consisting of the compound according to claim 1 in which R is allyl ii and its acid salts. CH 9 CNH SR 5. A compound selected from the group consisting of I the compound according to claim 1 m WhlCh R is N CCl and its acid salts. 

1. A COMPOUND OF THE STRUCTURE
 2. A compound selected from the group consisting of the compound according to claim 1 in which R is -CN and its acid salts.
 3. A compound selected from the group consisting of the compound according to claim 1 in which R is 5-tetrazolyl and its acid salts.
 4. A compound selected from the group consisting of the compound according to claim 1 in which R is allyl and its acid salts.
 5. A compound selected from the group consisting of the compound according to claim 1 in which R is -CCl3 and its acid salts. 